Efficacy of tigecycline monotherapy versus combination therapy with other antimicrobials against carbapenem-resistant Acinetobacter baumannii sequence type 2 in Heilongjiang Province.

BACKGROUND Selecting alternative antibiotic combinations as treatment options may help successfully manage carbapenem-resistant Acinetobacter baumannii (CRAB). This study aimed to determine the synergistic effects of tigecycline (TIG) monotherapy versus combination therapy with other antimicrobials against CRAB. METHODS After performing biochemical identification assays, we detected oxacillin-hydrolyzing (OXA)-type carbapenemase genes in 35 CRAB isolates. The minimum inhibitory concentrations (MICs) and interactions of the test drugs were determined using the checkerboard assay with TIG, colistin (CST) and meropenem (MEM). Static time-kill assays were conducted to validate the synergistic effects of the most efficacious combination. RESULTS The chromosomal gene, blaOXA-51-like, was tested among all isolates, blaOXA-23-like and blaOXA-24-like were present in 91.4% and 25.7%, respectively. In the checkerboard assay, the combination of TIG and MEM displayed the highest rate of synergy (30.5%) against the 35 isolates. In contrast, the TIG-CST combination showed a higher indifference interaction rate (36.1%) than that of the TIG-MEM (16.7%) combination. Antagonism appeared in one isolate for the TIG-CST combinations. The static time-kill assays confirmed the superior synergistic effect of CST against the CRAB isolates. CONCLUSIONS TIG combined with CST exhibited early synergistic activity that was not sustained beyond 12 h. TIG combination therapy can only be recommended when other optimized therapeutics are unavailable.

[1]  H. Seifert,et al.  Comparison of tigecycline susceptibility testing methods for multidrug-resistant Acinetobacter baumannii. , 2018, Diagnostic microbiology and infectious disease.

[2]  D. O’Callaghan,et al.  New Delhi Metallo-β-Lactamase-Producing Carbapenem-Resistant Enterobacteriacae Isolated From Bronchial Washings. , 2017, Irish medical journal.

[3]  R. Moniri,et al.  Sensitivity of levofloxacin in combination with ampicillin-sulbactam and tigecycline against multidrug-resistant Acinetobacter baumannii , 2017, Iranian journal of microbiology.

[4]  Wen-Sen Lee,et al.  Comparison of the clinical efficacy between tigecycline plus extended-infusion imipenem and sulbactam plus imipenem against ventilator-associated pneumonia with pneumonic extensively drug-resistant Acinetobacter baumannii bacteremia, and correlation of clinical efficacy with in vitro synergy tests. , 2016, Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi.

[5]  Neang S. Ly,et al.  Combinatorial pharmacodynamics of polymyxin B and tigecycline against heteroresistant Acinetobacter baumannii. , 2016, International journal of antimicrobial agents.

[6]  S. Jeong,et al.  In Vitro Interactions of Antibiotic Combinations of Colistin, Tigecycline, and Doripenem Against Extensively Drug-Resistant and Multidrug-Resistant Acinetobacter baumannii , 2015, Annals of laboratory medicine.

[7]  Yiyu Deng,et al.  Efficacy and safety of tigecycline for the treatment of severe infectious diseases: an updated meta-analysis of RCTs. , 2015, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[8]  Mathias W Pletz,et al.  Three Dimensional Checkerboard Synergy Analysis of Colistin, Meropenem, Tigecycline against Multidrug-Resistant Clinical Klebsiella pneumonia Isolates , 2015, PloS one.

[9]  C. Nikam,et al.  Molecular characterization of carbapenem-resistant Enterobacteriaceae at a tertiary care laboratory in Mumbai , 2015, European Journal of Clinical Microbiology & Infectious Diseases.

[10]  C. Doern,et al.  When Does 2 Plus 2 Equal 5? A Review of Antimicrobial Synergy Testing , 2014, Journal of Clinical Microbiology.

[11]  H. Giamarellou,et al.  Multidrug-resistant and extensively drug-resistant Gram-negative pathogens: current and emerging therapeutic approaches , 2014, Expert opinion on pharmacotherapy.

[12]  D. Nicolau,et al.  In Vitro Pharmacodynamics of Polymyxin B and Tigecycline Alone and in Combination against Carbapenem-Resistant Acinetobacter baumannii , 2013, Antimicrobial Agents and Chemotherapy.

[13]  A. MacGowan,et al.  Tigecycline pharmacokinetic/pharmacodynamic update. , 2008, The Journal of antimicrobial chemotherapy.

[14]  L. Dijkshoorn,et al.  An increasing threat in hospitals: multidrug-resistant Acinetobacter baumannii , 2007, Nature Reviews Microbiology.

[15]  M. Kaufmann,et al.  The role of ISAba1 in expression of OXA carbapenemase genes in Acinetobacter baumannii. , 2006, FEMS microbiology letters.

[16]  W. Hillen,et al.  Comparison of tetracycline and tigecycline binding to ribosomes mapped by dimethylsulphate and drug-directed Fe2+ cleavage of 16S rRNA. , 2004, The Journal of antimicrobial chemotherapy.

[17]  P. Patsalos,et al.  The Importance of Drug Interactions in Epilepsy Therapy , 2002, Epilepsia.

[18]  A. Apisarnthanarak,et al.  Comparative efficacy and safety of treatment options for MDR and XDR Acinetobacter baumannii infections: a systematic review and network meta-analysis , 2018, The Journal of antimicrobial chemotherapy.

[19]  M. Kollef,et al.  Secular trends in Acinetobacter baumannii resistance in respiratory and blood stream specimens in the United States, 2003 to 2012: A survey study. , 2016, Journal of hospital medicine.

[20]  AZLr TZPr,et al.  Synergistic Effect of Membrane-Active Peptides Polymyxin B and Gramicidin S on Multidrug-Resistant Strains and Biofilms of Pseudomonas aeruginosa , 2015 .